The goal of this proposal is to characterize chloride transport processes in large nerve and muscle cells. Of particular interest is the relationship between chloride transmembrane movements and intracellular pH regulation. We intend to study the possibility that an acid internal pH causes the chloride carrier is changed so that it begins to favor biocarbonate, thus initiating C1 /HCO-3 exchange. Another issue is the role of the sodium gradient in the Na-Cl co-transport system in the squid axon. Both Na and ATP are required for Cl influx and it is well-known that cellular chloride content is higher than expected equilibrium considerations. This will be studied by measuring intracellular chloride ion activity changes in axons predialyzed to a low chloride leve. The sodium gradient will be changed by varying either internal or external sodium concentrations.